Dillinger Jean-Guillaume, Maher Vincent, Vitale Cristiana, Henry Patrick, Logeart Damien, Manzo Silberman Stephane, Allée Guillaume, Levy Bernard I
From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.).
Hypertension. 2015 Dec;66(6):1138-44. doi: 10.1161/HYPERTENSIONAHA.115.06091. Epub 2015 Sep 21.
Treatment of hypertensive patients with β-blockers reduces heart rate and decreases central blood pressure less than other antihypertensive drugs, implying that reducing heart rate without altering brachial blood pressure could increase central blood pressure, explaining the increased cardiovascular risk reported with β-blocker. We describe a randomized, double-blind study to explore whether heart rate reduction with the If inhibitor ivabradine had an impact on central blood pressure. We included 12 normotensive patients with stable coronary artery disease, heart rate ≥70 bpm (sinus rhythm), and stable background β-blocker therapy. Patients received ivabradine 7.5 mg BID or matched placebo for two 3-week periods with a crossover design and evaluation by aplanation tonometry. Treatment with ivabradine was associated with a significant reduction in resting heart rate after 3 weeks versus no change with placebo (-15.8±7.7 versus +0.3±5.8 bpm; P=0.0010). There was no relevant between-group difference in change in central aortic systolic blood pressure (-4.0±9.6 versus +2.4±12.0 mm Hg; P=0.13) or augmentation index (-0.8±10.0% versus +0.3±7.6%; P=0.87). Treatment with ivabradine was associated with a modest increase in left ventricular ejection time (+18.5±17.8 versus +2.8±19.3 ms; P=0.074) and a prolongation of diastolic perfusion time (+215.6±105.3 versus -3.0±55.8 ms with placebo; P=0.0005). Consequently, ivabradine induced a pronounced increase in Buckberg index, an index of myocardial viability (+39.3±27.6% versus -2.5±13.5% with placebo; P=0.0015). In conclusion, heart rate reduction with ivabradine does not increase central aortic blood pressure and is associated with a marked prolongation of diastolic perfusion time and an improvement in myocardial perfusion index.
URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004779-35.
与其他抗高血压药物相比，用β受体阻滞剂治疗高血压患者可降低心率，但降低中心血压的作用较小，这意味着在不改变肱动脉血压的情况下降低心率可能会升高中心血压，这解释了β受体阻滞剂报告的心血管风险增加的原因。我们描述了一项随机、双盲研究，以探讨用If抑制剂伊伐布雷定降低心率是否会对中心血压产生影响。我们纳入了12例患有稳定冠状动脉疾病、心率≥70次/分钟（窦性心律）且接受稳定背景β受体阻滞剂治疗的血压正常患者。患者采用交叉设计，接受伊伐布雷定7.5mg每日两次或匹配的安慰剂治疗，为期两个3周疗程，并通过平面眼压测量法进行评估。与安慰剂组心率无变化相比，伊伐布雷定治疗3周后静息心率显著降低（-15.8±7.7对+0.3±5.8次/分钟；P=0.0010）。中心主动脉收缩压变化（-4.0±9.6对+2.4±12.0mmHg；P=0.13）或增强指数（-0.8±10.0%对+0.3±7.6%；P=0.87）在组间无相关差异。伊伐布雷定治疗与左心室射血时间适度增加（+18.5±17.8对+2.8±19.3毫秒；P=0.074）和舒张期灌注时间延长（+215.6±105.3对安慰剂组的-3.0±55.8毫秒；P=0.0005）有关。因此，伊伐布雷定使Buckberg指数（心肌活力指数）显著增加（+39.3±27.6%对安慰剂组的-2.5±13.5%；P=0.0015）。总之，伊伐布雷定降低心率不会升高中心主动脉血压，且与舒张期灌注时间显著延长和心肌灌注指数改善有关。
网址：https://www.clinicaltrialsregister.eu。唯一标识符：2011-004779-35。
